Evidence of a novel role for Pygopus in ribosomal RNA transcription

Increased protein synthesis during cell proliferation is accompanied by a compensatory increase in efficient ribosome production, but the mechanisms by which cells adapt to this requirement are not fully understood. Here, we present evidence that Pygopus, a protein originally identified as a core component of the Wnt/β-catenin transcription complex is also involved in ribosomal (r)RNA transcription during cancer cell growth. Pygopus was detected in the nucleoli of several transformed cell lines and was associated with Treacle and UBF, proteins essential for ribosome biogenesis in development and cancer. Pygopus was also detected at the ribosomal gene promoter along with core components of the rDNA transcription complex. RNAi-mediated depletion of hPygo2 reduced Histone H4 acetylation at the rDNA promoter, downregulated rRNA production and induced growth arrest in both p53 positive and negative cells. In p53 positive cells, hPygo2 knockdown triggered the ribosomal stress pathway, culminating in p53-dependent growth arrest at G1 of the cell cycle. Our results suggest a novel involvement of Pygopus in the promotion of rRNA transcription in cancer cells.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Disease Source Type: research